The investigational CD40L antagonist improved systemic disease activity at 48 weeks, with Amgen reporting an effect as early as week four.
Dazodalibep has met its primary endpoint in a phase 3 trial of patients with moderate-to-severe systemic Sjögren’s disease, according to topline results released by manufacturer Amgen.
The OASIZ 301 trial found treatment with the investigational CD40 ligand antagonist fusion protein produced a statistically significant and clinically meaningful improvement in systemic disease activity at week 48 compared with placebo.
The primary endpoint was change from baseline in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), which measures disease activity across multiple organ systems.
Amgen said improvements in ESSDAI were evident from week four and were sustained through week 48. However, the company has not yet released the magnitude of the treatment effect or detailed efficacy data, with full results due to be presented at an upcoming medical meeting.
OASIZ 301 was a randomised, double-blind, placebo-controlled study involving approximately 621 adults with Sjögren’s disease and moderate-to-severe systemic disease activity, defined as an ESSDAI score of at least five.
Secondary endpoints included dryness, fatigue, tender and swollen joints, and ESSDAI response, defined as a reduction of at least five points from baseline. Results for those endpoints were not included in the topline announcement.
Lead investigator Dr Ghaith Noaiseh, associate professor of medicine in allergy, clinical immunology, and rheumatology at the University of Kansas Medical Centre, said the results supported further investigation of the drug.
“Patients with Sjögren’s disease contend with debilitating symptoms and systemic manifestations for which no approved disease-modifying therapy exists,” he said.
“These topline results provide further support for dazodalibep as an emerging treatment for improving systemic disease activity and represent an important advance for the field.”
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The most common adverse events occurring in at least 5% of patients and at a higher rate with dazodalibep than placebo were nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions.
In a statement, Amgen said these were generally mild to moderate. Discontinuations due to adverse events were uncommon and balanced between treatment groups, while there was no observed imbalance in thromboembolic events or opportunistic infections.
Dazodalibep is a potential first-in-class CD40L antagonist fusion protein designed to disrupt interactions between T cells, B cells, and other antigen-presenting cells, thereby targeting immune activation.
The drug is being investigated in two Sjögren’s populations: patients with moderate-to-severe systemic disease, and those with a high symptom burden but low systemic disease activity.
The latter population is being studied in the phase 3 OASIZ 303 trial, which is expected to complete in the fourth quarter of 2026.
Amgen is also running OASIZ 304, an open-label extension evaluating the long-term safety and tolerability of dazodalibep in eligible participants from both phase 3 studies.
Dr Jay Bradner, executive vice president, Research and Development, Artificial Intelligence and Data at Amgen, said the results marked an “important step forward for people living with Sjögren’s disease, a condition with significant unmet need and no approved systemic treatment options”.
“The rapid and sustained improvement observed in systemic disease activity reinforces our confidence in dazodalibep and the broader Phase 3 program as we work to deliver a new, highly differentiated option for people living with this debilitating autoimmune disease,” he said.
The OASIZ 301 findings remain preliminary, with detailed efficacy and safety results yet to be released.
